Vexas Syndrome: A Multisystem Challenge with Sweet Syndrome and Myelodysplastic Syndrome

VEXAS (vacuoles, E1 enzyme, x-linked, autoinflammatory, somatic) syndrome, is a recently described autoinflammatory condition caused by UBA1 gene mutations. It can present with both sweet syndrome (SS) and myelodysplastic syndrome (MDS). SS, or acute febrile neutrophilic dermatosis, is an inflammatory disorder characterised by fever, neutrophilia and painful erythematous plaques. MDS is a clonal haematopoietic stem cell disorder.

We present a case of a 43-year-old Arab male with a history of MDS. He presented with painful, non-pruritic, non-haemorrhagic skin lesions. The patient also reported having fever and chills, partially relieved by antipyretics. Bone marrow aspiration was done and revealed a 'dry tap' which was inadequate for evaluation. Immunophenotyping of bone marrow biopsy was consistent with MDS. A skin biopsy of the lesions was performed and confirmed sweet syndrome. The patient was treated with methylprednisolone 500 mg daily for five days, with a significant improvement in clinical symptoms. After stabilisation, treatment for MDS was started with 200 mg IV azacitidine daily for seven days.

Given the patient's age, gender, MDS diagnosis and atypical presentation of sweet syndrome, VEXAS syndrome is a strong possibility. Further investigation, including genetic testing for a UBA1 mutation, is warranted. A diagnosis of VEXAS syndrome would significantly impact long-term management and prognosis, as it was determined to be important in reducing the recurrence rate of sweet syndrome.

Features such as steroid-dependent skin lesions, cytopenias and MDS raise suspicion for VEXAS syndrome - a systemic autoinflammatory disorder linked to UBA1 mutations and clonal haematopoiesis. Despite lacking genetic confirmation, the patient responded to high-dose steroids and azacitidine, underscoring the need for UBA1 testing to guide management and prognosis in overlapping MDS-inflammatory syndromes.Sweet syndrome is not always just cutaneous; when it clusters with MDS and systemic inflammation, VEXAS becomes an important diagnostic consideration.